The primary goal of this proposal is to better understand electrical stimulation. 1) The first specific aim is to calculate the strength-interval curve. The strength-interval curve plays an important role in determining the excitability of cardiac tissue. Preliminary studies suggest that the shape of the strength-interval curve is determined by a complex interaction between the spatially inhomogeneous transmembrane potential distribution and the nonlinear properties of the membrane ionic channels. A hypothesis is that more sophisticated models of cardiac tissue also lead to similar shaped strength-interval curves. Experiments show that the strength-interval curve changes with time after an electrode is implanted in the heart. A hypothesis is that tissue damage around the electrode causes the anodal strength-interval curve to shift to larger intervals with time. 2) The second specific aim is to clarify the mechanism of reentry induction. Preliminary studies predict that a modification of the tissue refractory period arising from the inhomogeneous transmembrane potential distribution around a stimulating electrode causes reentry, but that the reentrant wave front is not stable. A hypothesis is that a better model of cardiac tissue will predict a stable, reentrant pattern. 3) The third specific aim is to determine how electroporation will affect stimulation thresholds and reentry. During electrical stimulation from a unipolar electrode, the transmembrane potential can reach levels at which electroporation occurs. A hypothesis is that electroporation will change the cathodal threshold to a greater extent than the anodal threshold. 4) The fourth specific aim is to calculate the strength-interval curves for biphasic stimulation. A hypothesis is that biphasic stimulation will affect "break" stimulation to a greater extent than "make" stimulation. 5) The fifth specific aim is to determine the effect of inhomogeneities on unipolar stimulation of cardiac tissue. Computer simulations based on the bidomain model will be used to achieve these specific aims and test these hypotheses.